Novel fragrance materials chemical intermediates and processes

ABSTRACT

NOVEL ALDEHYDES HAVING THE STRUCTURE:   2-(HCO-C(-R1)(-R2)-(CH2)N-),7,7-DI(CH3-)-2-NORPINENE   WHEREIN R1 IS HYDROGEN OR LOWER ALKYL, R2 IS LOWER ALKYL, AND N IS 1 OR 2; LOWER ALKYL ACETALS THEREOF; LOWER ALKYLENE ACETALS THEREOF; MIXTURES AND OLFACTORY COMPOSITIONS CONTAINING SAME; MIXTURES AND OLFACTORY COMPOSITIONS CONTAINING 6.6 DIMETHYL BICYCLO (3.1.1.)HEPT-2-ENE-ALKANALS (HEREINAFTER REFERRED TO AS PINOALKANALS) HAVING THE STRUCTURE:   2-(HCO-CH2-(CH2)N-),7,7-DIMETHYL-2-NORPINENE   WHEREIN N IS 1 OR 2; LOWER ALKYL ACETALS THEREOF; LOWER ALKYLENE CYCLIC ACETALS THEREOF; NOVEL PROCESSES FOR THE PRODUCTION OF SUCH CHEMICAL COMPOUNDS; AND SCHIFF BASES OF SAID ALDEHYDES AND PINOALKANALS.

3,636,113 NOVEL FRAGRANCE MATERIALS, CHEMICAL INTERMEDIATES, ANDPROCESSES John B. Hall, Rumson, N.J., assignor to International Flavors& Fragrenees, Inc., New York, N.Y N Drawing. Filed Nov. 4, 1969, Ser.No. 874,038 Int. Cl. C07c 119/00 US. Cl. 260566 R 1 Claim ABSTRACT OFTHE DISCLOSURE Novel aldehydes having the structure:

m Hz wherein n is l or 2; lower alkyl acetals thereof; lower alkylenecyclic acetals thereof; novel processes for the production of suchchemical compounds; and Schiif bases of said aldehydes and pinoalkanals.

BACKGROUND OF THE INVENTION There is a continuing search for materialshaving desirable fragrances. Such materials are sought either to fortifyweak natural materials, to obviate weaknesses of natural materials, orto provide new fragrance or perfume types which have not heretofore beenavailable. Such substances desirably have stability in a wide variety ofperfumed articles and perfume compositions, are easily manufactured andhave intense aromas.

It is known to carry out a two-step reaction wherein myrtenol is reactedwith methyl vinyl ether in the presence of mercuric acetate as aCatalyst in order to obtain the vinyl ether of myrtenol; and wherein theresulting vinyl ether is then rearranged to form an aldehyde having thestructure:

CH2C\ a H The compound so formed is relatively uninteresting from thestandpoint of perfumery (see Julia et al. Bull. Soc. Chim., 1962,1947-1952).

Furthermore, it is known to react nopol (pinomethanol) with phosphorouspentachloride to form a compound of the structure:

CHQCHQCI nited States Patent 0 F Patented Jan. 18, 1972 'ice then toform the corresponding Grignard reagent from the nopol derivative usingmagnesium and react the Grignard reagent with triethoxy methane to form6,6 dimethyl bicyclo[3.1.1]hept-2-ene-2-propanol (hereinafter referredto as pinoacetaldehyde) having the structure:

iZ Z V (See Bull. Soc. Chim., France, 1955, l3991408). This compound washeretofore recognized only as an intermediate for the production ofother chemical compounds, and was not known or disclosed for perfumeuses. It is also known to react acrolein with beta-pinene to form 6,6dimethyl bicyclo[3.l.l]hept-2-ene-2-n-butanal (hereinafter referred toas pinopropionaldehyde). See Kruk et a1., Recl. Trav. Chim. Pays-Bas.1969, 88(2), (l3948). As in the case of pinoacetaldehyde, thepinopropionaldehyde was heretofore not recognized as being useful as aperfume ingredient.

THE INVENTION The invention comprises the novel products, the novelprocesses and steps of processes according to which such products aremanufactured, as well as the use in perfumery of the said novel productsand known lower homologues thereof, specific embodiments of which aredescribed hereinafter by way of example and in accordance with which itis now preferred to practice the invention.

Briefly, the present invention provides the novel pinane derivatives,alpha-alkyl and alpha, alpha-dialkyl6,6 dimethyl bicyclo[3.1.l]hept-2-ene-alkanals, (hereinafter referred to asalpha-substituted pinoacetaldehydes) having the formulae:

wherein R is hydrogen or lower alkyl; R is lower alkyl, and n is 1 or 2as well as the corresponding lower alkyl acetals having the structure:

wherein R and R are the same or different lower alkyl groups, andwherein n is l or 2 and lower alkylene'cyclie acetals having thestructure wherein R is lower alkylene. The invention also con templatesperfume and fragrance materials containing such compounds, as well asthe known lower homologues thereof. The materials found to be useful inthe instant invention are produced by several novel methods:

(I) One such method involves reacting pinocarveol with a substituted orunsubstituted ethyl vinyl ether in the presence of a protonic acid suchas phosphoric acid with or without a suitable additional inert reactionvehicle. When ethyl vinyl ether is used, the reaction product ispinoacetaldehyde. When the vinyl group is alkyl or dialkyl substitutedin the beta-position, the reaction product is one of the novel productsof this invention. The reaction can be represented as follows:

Dialkyl acetals of the above-mentioned aldehydes can be formed byreaction thereof with ethyl orthoformate or alcohols in the presence ofan acid catalyst. Alkylene cyclic acetals of the above-mentionedaldehydes can be produced by reaction thereof with a lower alkyleneglycol such as ethylene glycol or propylene glycol.

(II) In another method, a Schiif base is formed by reacting a suitablysubstituted or unsubstituted acetaldehyde with a primary amine such as alower alkyl amine or cycloalkyl amine, for example cyclohexyl amine,thus:

The resulting Schiff base is reacted with a Grignard reagent such asmethyl magnesium chloride and reacting the resulting salt with amyrtenyl halide such as myrtenyl chloride, myrtenyl bromide, or thelike, thus:

The resulting Schitf base, a novel chemical compound, is then hydrolyzedin situ (preferably using an aqueous acid such as sulfuric acid) to formthe desired pinoacetaldehyde, or alpha-substituted or alpha,alpha-disubstituted pinoacetaldehyde. The general technique applied toalkylation of aldehydes is disclosed by Stork and Dowd at 85 J. Am.Chem. Soc. 21782l80 [July 20, 1963]. The acetals and cycliacetals of theaforementioned aldehydes, again, may be formed as desired as above. Itwill be understood from the present disclosure pinoacetaldehydecompounds, can be obtained in more than one stereoiso meric form andthat these stereoisomers are intended to be included in the formulasshown.

It has been found that the known pinoalkanals and the novelalpha-substituted and alpha, alpha-disubstituted pinoalkanals and theirlower alkyl acetals and lower alkylene cycliacetals of this inventionpossess a fresh, green aroma, part woodsy, part flowery, ozone-like andreminiscent of early morning dew-laden vegetation. The lower homologs(eg the pinoacetaldehyde and pinopropionaldehyde and their lower alkylacetals) are more pungent and the higher (eg. pinoisobutyraldehyde)unexpectedly softer and more floral; all exhibiting good persistence.This fragrance quality particularly makes pinalkanals including thenovel alphaalkyl and alpha, alpha-dilkyl pinolkanals and their acetalsand cyclic acetals suitable for incorporation into perfume compositionsand fragrance modifying compositions wherein a fresh air fragrancecharacter is desirable. The intensity and other properties ofpinoalkanals including the novel substituted pinoalkanals and acetals ofthis invention are sufiiciently marked so that they can be employedeither as purified materials or in admixture, or in mixtures of lesserpurity as obtained by the novel reactions herein described.

Several pinoalkanals including the novel alpha-alkyl and alpha,alpha-dialkyl pinoalkanals may be conveniently produced from the knownmaterial pinocarveol which latter material can be obtained by theprocess described in the United States application of Peter W. D.Mitchell, Ser. No. 732, 539 filed on May 28, 1968, in which betapineneis reacted with hydrogen peroxide and a small amount of seleniumdioxide.

One of the reactions of this invention involves a conversion ofpinocarveol to yield substantial quantities of the substituted orunsubstituted pinoalkanals. The reaction is carried out with thesubstituted or unsubstituted alkyl vinyl ethers in the presence of aprotonic acid.

The reaction product formed is dependent upon the particular substitutedalkyl vinyl ether of the formula where A is lower alkyl, R is hydrogenor lower alkyl and R is hydrogen or lower alkyl. The following alkylvinyl ethers will yield the indicated reaction products:

(1) Alkyl vinyl ether Reaction product Ethyl vinyl ether Ethyl(Z-rnethyl-lpropenyl) other.

Ethyl (2-cthyl-l butcnyl) other.

Ethyl (Z-methyl-lpentenyl) ether.

The preferred protonic acid is phosphoric acid. In order to effect thereaction, from 0.005% up to 2% and preferably from 0.01% up to about0.5% (by weight of the reaction mass) of protonic acid should be used.The reaction is preferably carried out at superatmospheric pressures.The best results have been obtained with reaction pressures in the rangeof from about three to about seven atmospheres and temperatures in therange of -170 C. The amount of reactants used can vary over wide limits,and preferably the alkyl vinyl ether reactant is present in excess.Preferably, the molar ratio of ether to pinocarveol is from 1.5:1 up toabout 2.5 :1. At the termination of the reaction which may proceed for aperiod of from one hour up to three hours (depending on the temperatureof reaction and the yield desired), the excess vinyl ether reactant isstripped off and the substituted or unsubstituted pinoacetaldehyde isdistilled usually under reduced pressures. This first reaction sequenceis preferred for the production of unsubstituted pinoacetaldehyde.

A second reaction sequence may also be used for the production ofseveral pinoalkanals. This method can be practiced step-by-step asfollows:

(1) Production of the Schiff base of an aldehyde. In producing theSchiff base, any aldehyde may be used which has an available u-hydrogenand any primary amine can be used. Thus, in producingpinoisobutyraldehyde, for example, the aldehyde used would beisobutyraldehyde. In producing pinoisopropionaldehyde, the aldehyde usedwould be propionaldehyde. In production of the Schiff base, the use ofequimolar amounts of amine and aldehyde is desirable; use of an excessof either ingredient giving rise to unnecessary added cost. Preferablythe temperature of reaction is from 10 C. up to 30 C.

(2) Production of a Schiff base-Grignard reagent. after drying, theSchiff base produced in (l) is reacted with any convenient, inexpensive,readily available Grignard reagent, preferably a lower alkyl magnesiumhalide such as methyl magnesium chloride in the presence of a suitableinert solvent such as tetrahydrofuran. The quantity of the methylmagnesium chloride or other Grignard reagent should be in slight molarexcess to insure completion of the reaction. The preferred excess ofGrignard reagent is of the order of 5-l0%. The reaction should takeplace at a temperature in the range of from about 50 C. to about 80 C.

(3) Addition of the myrtenyl moiety and hydrolysis. At the completion ofthe reaction of (2), myrtenyl chloride or myrtenyl bromide is added tothe Schiff base- Grignard material so produced. It is preferred that themyrtenyl halide be in molar excess with respect to the Schiffbase-Grignard material. This reaction is carried out preferably atatmospheric pressure. The preferred temperature range for this reactionis from about 50 C. to 80 C. The product is the Schiff base of thedesired substituted or unsubstituted pinoacetaldehyde. The Schiff baseso produced is hydrolyzed in any suitable readily available aqueousacid, such as sulfuric acid in order to form the desired substituted orunsubstituted pinoacetaldehyde. The products of the foregoing reactionscan be neutralized, washed and purified to yield a pure product.Purification can be carried out by conventional methods such asextraction, chromatography, distillation and the like.

The substituted and unsubstituted pinoalkanals and corresponding acetalsof this invention can be incorporated into a wide variety ofcompositions which will be enhanced by their flowery, ozone-like, woodsynotes. As noted above, the novel materials, as well as the knownpinoacetaldehyde and pinopropionaldehyde, can be added to perfumecompositions in the pure form or in admixture with one another. They canbe added to mixtures of materials in fragrance-modifying compositions toprovide a desired fragrance character to a finished perfume material orother article. A fragrance-modifying composition is one which does notof itself provide a total fragrance impression (as would a perfumecomposition), but it alters and enhances, reinforces or fortifiesanother composition to provide a finished perfume or overall fragrance.

The perfume and fragrance compositions obtained according to thisinvention are suitable in a wide variety of perfumed articles and canalso be used to enhance, modify or reinforce natural fragrancematerials. It will thus be appreciated that pinoacetaldehyde,pinopropionaldehyde and substituted pinoalkanals, and acetals thereof ofthis invention are useful as olfactory agents and fragrances.

The term perfume composition is used herein to mean a mixture ofcompounds, including, for example, natural oils, synthetic oils,alcohols, other aldehydes, ketones, esters, lactones, and frequentlyhydrocarbons which are admixed so that the combined odors of theindividual components produce a pleasant or desired fragrance. Suchperfume compositions usually contain: (a) the main note or the bouquetor foundation-stone of the composition; (b) modifiers which round offand accompany the main note; (c) fixatives which include odoroussubstances which lend a particular note to the perfume throughout allstages of evaporation, and substances which retard evap- Cit oration;and (d) top-notes which are usually low-boiling fresh-smellingmaterials. Such perfume compositions or the novel materials of thisinvention can be used in conjunction with carriers, vehicles, solvents,dispersants, emulsifiers, surface-active agents, aerosol propellants,and the like.

In perfume compositions the individual components contribute theirparticular olfactory characteristics, but the overall effect of theperfume composition will be the sum of the effect of the eachingredient. Thus, the substituted and unsubstituted pinoacetaldehydesand acetals thereof of this invention can be used to alter the aromacharacteristics of a perfume composition, for example, by highlightingor moderating the olfactory reaction contributed by another ingredientof the composition.

The amount of pinoalkanal or alpha-substituted and disubstitutedpinoalkanals or acetals thereof of this invention which will beeffective in perfume compositions depends on many factors, including theother ingredients, their amounts and the effects which are desired. Ithas been found that perfume compositions containing as little as 3.0% byweight of mixtures or compounds of this invention, or even less can beused to impart a fresh air flowery odor to soaps, cosmetics and otherproducts. They are well suited to use in the preparation of lavenderfragrances. The amount employed will depend on considerations of cost,nature of the end product, the effect desired in the finished product,and the particular fragrance sought. All parts, proportions,percentages, and ratios herein are by weight, unless otherwiseindicated.

The substituted or unsubstituted pinoalkanals or acetals disclosedherein, mixtures thereof, and reaction mixtures containing them can beused alone, in a fragrance-modifying composition, or in a perfumecomposition as an 01- factory component in detergents and soaps; spacedeodorants; perfumes; colognes; bath preparations such as bath oil, bathsalts; hair preparations such as lacquers, brilliantines, pomades, andshampoos; cosmetic preparations such as creams, deodorants, handlotions, sun screens; powders such as talcs, dusting powders, facepowder and the like. When the pinoalkanals or acetals of this inventionare used in perfumed articles such as the foregoing they can be used inamounts of 0.1% or lower. Generally it is preferred not to use more thanabout 1.0% in the finished perfumed article, since the use of too muchwill tend to unbalance the total aroma and will needlessly raise thecost of the article.

The following examples serve to illustrate embodiments of the inventionas it is now preferred to practice it. It will be understood that theseexamples are illustrative and the invention is to be consideredrestricted thereto only as indicated in the appended claims.

EXAMPLE I Preparation of 'pinoacetaldehyde by reaction of pinocarveolwith ethyl vinyl ether 'Into a 1-liter autoclave the followingingredients were placed:

G. Pinocarveol 250 Ethyl vinyl ether 250 phosphoric acid 0.5

The contents of the autoclave were heated at a temperature range of 155C. over a period of 2% hours. The pressure within the autoclave was inthe range of 7080 p.s.i.g. At the termination of the reaction thecontents of the autoclave were removed and the organic phase was washedwith an equal volume of 5% of sodium bicarbonate and then with an equalvolume of water. The excess ethyl vinyl ether was stripped off and theresulting crude product was distilled at 84-88 C. on a 12 Goodloe column(pressure: 2.8-3.2 mm. Hg; reflux ratio 9:1).

Infra red, NMR and mass spectral analysis confirmed the followingstructure of the product:

CH CH C The pinoacetaldehyde thus formed had a highly persistent, veryfresh, pungent, flowery, woodsy, ozone-like odor reminiscent of earlymorning dew-laden vegetation.

EXAMPLE II The preparation of pinoisobutyraldehyde (a) Formation ofSchifi base.-396 g. (4.0 moles) of cyclohexylamine was placed in a1-liter flask. Over a period of one hour, while maintaining thetemperature at 20 C., 292 g. of isobutyraldehyde was added. At the endof the addition period, the aqueous and organic phases were separatedand the organic phase consisting of the Schiff base N(2-methylpropylidene) cyclohexylamine was dried over magnesium sulfate anddistilled at a vapor temperature of 6167 C. (pressure: 13-14 mm. Hg);

(b) Reaction of Schiff base with Grignard reagent.- Into a 3-liter flaskpurged with nitrogen, 680 ml. (2.02 moles) of methyl magnesium chloridein tetrahydrofuran was added. The contents of the flask were heated to60 C. Over a period of 1 hour, 282 g. of the Schiif base produced inPart (a) was added, maintaining the temperature in the range of 50 C.70C. After addition, the com tents were heated for 4 hours until theevolution of hydrogen ceased;

(0) Reaction of the Schiff baseGrignard Reagent with myrtenylchloride.Over a period of 2 hours 444 g. of 71.3% (wt.) myrtenylchloride were added to the reaction product produced in part (b), Whilemaintaining the temperature in the range of 65-70 C. After addition wascompleted, the reaction mass was stirred for a period of 8 hours,maintaining the temperature in the range of 60-72 C.;

(d) Hydrolysis of Schiif base product formed in (c).The pH of thereaction mass was brought to 4 by addition 1,140 g. of 10% aqueoussulfuric acid. The mass was then heated for a perioid of thirty minutesat 65 C. after which the aqueous phase was separated from the organicphase. The aqueous layer was extracted with 550 ml. of toluene and thetoluene extract was bulked with the organic layer. The organic psase wasthen washed per the following sequence:

(a) One 550 ml. volume of aqueous hydrochloric acid;

(b) One equal volume of saturated sodium chloride solution;

(0) One equal volume of a 3% sodium bicarbonate solution (bringing thepH to 8.0);

(d) One equal volume of a saturated sodium chloride solution [bringingthe pH to 7.0].

The solvent Was then stripped oil and the reaction product was distilledin a 12-inch Goodloe column at a vapor temperature of 9194 C.[pressure:2.63.0 mm. Hg:refiux ratio 9: l]. 236 g. of the reactionproduct, alphapinyl isobutyraldehyde was recovered, the structure ofwhich, confirmed by NMR, infrared and mass spectral analysis was asfollows:

The alpha-pino-isobutyraldehyde had a highly persistent, fresh, softfloral, woodsy, ozone-like odor reminiscent of early morning dew-ladenvegetation.

EXAMPLE H1 The following mixture is prepared:

Ingredients: Parts by Wt. Coumarin 100 Linalol 200 Benzylacetate 50Geranium absolute 30 Methylacetophenone 50 Bergamot 40 Lavander, Barreme120 Pinoacetaldehyde (product of Ex. I} Benzophenone 25 Trichlorornethylphenyl carbinyl acetate 25 'Hydroxycitronellal 20 Sauge Sclaree 20Neroli bigarade 20 lsobutylsalicylate l0 Ylang-Ylang bourbon 10Patchouli oil 1O Vetiver acetate 5 Mousse de chene absolute 5 Anisalcohol 10 Basilicum absolute 5 A pleasing new fragrance results givingan interesting variation which can be described as a fresh-air qualityto the basic classic Foin Coup cologne blend.

EXAMPLE IV The following mixture is prepared:

Ingredients: Parts by wt. Coumarin Linalool 200 Benzylacetate 50Geranium absolute 30 Methylacetophenone 50 Bergamot 40 Lavander, Barremealpha-Pinoisobutyraldehyde (product of Ex. H)- 80 Benzophenone 25Trichloromethyl phenyl carbinyl acetate 25 Hydroxycitronellal 20 SaugeSchlaree 20 Neroli bigarade 20 Isobutylsalicylate 10 Ylang-Ylang,bourbon 10 Patchouli oil 10 Vetiveryl acetate 5 Mousse de chene absolute5 Anis alcohol 10 Basilicum absolute 5 A pleasing new fragrance resultsgiving an interesting variation which can be described as a fresh-air"quality to the basic classic Foin Coupe cologne blend.

It will be appreciated from the present description that thepinoalkanals and the novel substituted derivatives of pinoalkanals andacetals thereof can be included in other perfume compositions and inother perfumed articles such as detergents, shampoos, powders, soaps,deodorants, sachets, paper goods, and the like.

What is claimed is:

1. A Schifif base having the structure:

3,636,113 9 10 wherein R is hydrogen or lower alkyl, R is hydrogen orBERNARD HELPIN, Primary Examiner lower alkyl, R 1s lower alkyl orcyclohexyl, and n 1s 1 or 2. G. A SCHWARTZ, Assistant ExaminerReferences Cited Us, (:1, X,R

(1]93g1)siems Handbuch der Orgamsche Chenne, vol. VII 5 252 522; 26034O.7, 340.9, 611 F Page 1 of 3. UNITED STATES PATENT OFFICE CERTIFICATEOF CORRECTION Patent No. 636,113 Dated January 18, 1972 Inventor(s) JOHNB. HALL It is certified that error appears in the above-identifiedpatent and that said Letters Patent are hereby corrected as shown below:

001.2, line 10 The formula should read:

(.01. 3, line 55 the forrrllqula should read:

CH?-C-C: N

V Y I Page 2 of 3. UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTIONPatent No. 3 3 3 3 Dated January v 97 lnvento -(s) JOHN B. HALL It iscertified that error appears'in the above-identified patent and thatsaid Letters Patent are hereby corrected as shown below:

Col. 3, line 70 After disclosure insert -that some of thealpha-monoalkyl and alpha, alphadialkyl- Col. l, line 9 Changepinalkanals to --pinoalkanals- Col. L, line 10 Change "alpha-dilkyl" to-alphadialkyl-- Col. L, line 10 Change pinolkianals to -pinoall ;anals-Col. 4, line 35 The formula should read:

-- AO-C C Col. l, lines B/ L L- Column 2 of the Table should read:

Reacti til Product rather than Reaction product" Col. 5, line 11 Change"after" to After Col. 7, line M6 Change "perioid" to -period- Col. 7,line 5l Change psase" to -phase- Page 3 of 3. UNITED STATES PATENTOFFICE CERTIFICATE OF CORRECTION Patent No. 3,636,113 Dated January 18,1972 Inv n (s) JOHN B. HALL It is certified that error appears in theabove-identified patent and that said Letters Patent are herebycorrected as shown below:

Col. 8, Claim 1 The structure should read:

CH -c-c N 2 n H 3 Signed and sealed this hth day of July 1972.

(SEAL) Attest:

EDWARD M.FLETCHER,JR ROBERT GOTTSCHALK Attesting Officer Commissioner ofPatents

